Neurotransmitters

Composed By Muhammad Aqeel Khan
Date 15/9/2025

Neurotransmitters are the small chemical messengers that let brain cells (neurons) talk to one another. They shape everything from reflexes and movement to mood, learning, memory, sleep, and appetite. When this chemical language runs smoothly, we think, move, feel, and adapt. When it’s out of balance, it can lead to disorders ranging from depression and anxiety to Parkinson’s disease and epilepsy. This article explains what neurotransmitters are, how they work (synthesis → release → receptor binding → deactivation/reuptake), summarizes the major neurotransmitter systems (Dopamine, Serotonin, Acetylcholine, Norepinephrine, GABA, Glutamate), explores how imbalances affect health, and points to modern evidence and references.

What are neurotransmitters?

A neurotransmitter is a chemical released by a neuron to transmit a signal across a synapse (the tiny gap) to another neuron, muscle cell, or gland. Neurotransmitters can be simple amino acids (e.g., glutamate, GABA), monoamines (e.g., dopamine, serotonin, norepinephrine), acetylcholine, peptides (e.g., substance P), or gases (NO). They act on specific receptors on the receiving cell to produce excitatory, inhibitory, or modulatory effects. Broad reviews and physiology resources summarize their diversity and central roles in brain function.

How neurotransmission works — synthesis, release, receptor binding, and deactivation

Synthesis — Many neurotransmitters are synthesized in the neuron from dietary precursors. For example, dopamine is made from the amino acid tyrosine via tyrosine hydroxylase; serotonin is made from tryptophan via tryptophan hydroxylase; GABA is synthesized from glutamate by glutamic acid decarboxylase. Enzymes and vesicular transporters concentrate neurotransmitters into synaptic vesicles.
Release — When an action potential reaches the axon terminal it triggers voltage-dependent calcium channels to open. Calcium influx causes vesicles to fuse with the membrane and release neurotransmitter into the synaptic cleft (exocytosis). Some systems also signal via “volume transmission” where neuromodulators diffuse and act beyond classic synapses.
Receptor binding — Transmitters bind to two broad classes of receptors: ionotropic (fast, ligand-gated ion channels that change membrane potential immediately) and metabotropic (G-protein coupled receptors that modulate intracellular signaling and are slower but longer lasting). The same neurotransmitter often has multiple receptor subtypes that produce different effects depending on brain region and cell type.
Reuptake / Deactivation — After signaling, neurotransmitters are removed by reuptake transporters (e.g., SERT for serotonin, DAT for dopamine), enzymatic breakdown (e.g., monoamine oxidase, acetylcholinesterase), or diffusion. These termination mechanisms tightly control signal duration and are major targets for drugs (e.g., SSRIs block SERT; acetylcholinesterase inhibitors prolong acetylcholine).

Major neurotransmitters and their functions

Dopamine — reward, motivation, movement, cognition

Dopamine (DA) modulates reward learning, motivation, attention, and motor control. Dopaminergic neurons in the substantia nigra and ventral tegmental area are critical for movement and reward pathways. Loss of nigrostriatal dopamine causes Parkinson’s disease, while dysregulated dopamine signaling is implicated in schizophrenia, addiction, and some forms of mood disorder. Recent reviews emphasize dopamine’s diverse roles across brain circuits and emerging links to metabolic and cognitive processes.

Serotonin — mood, sleep, appetite, pain modulation

Serotonin (5-HT) regulates mood, anxiety, sleep, appetite, and some cognitive functions. The serotonergic system is a major target for antidepressants (SSRIs) that increase extracellular serotonin by blocking reuptake. However, modern systematic reviews show the relationship between serotonin levels and depression is complex and that the “simple low-serotonin” hypothesis is insufficient to explain depression fully — clinical benefit from SSRIs exists but mechanistic subtleties remain under research.

Acetylcholine — attention, learning, autonomic function

Acetylcholine (ACh) acts at neuromuscular junctions (peripheral) and in central cholinergic systems that support attention, arousal, memory encoding, and autonomic regulation. Cholinergic dysfunction contributes to cognitive deficits in Alzheimer’s disease; cholinesterase inhibitors are used to boost synaptic ACh in symptomatic treatment.

Norepinephrine (noradrenaline) — arousal, attention, stress responses

Norepinephrine (NE) from the locus coeruleus promotes arousal, vigilance, attention, and stress responses. It modulates signal-to-noise in cortical circuits and is targeted by certain antidepressants (SNRIs, tricyclics). Altered NE signaling is implicated in PTSD, ADHD, and mood disorders.

GABA — the main inhibitory transmitter

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain. By opening chloride channels (GABA-A) or activating G-protein coupled receptors (GABA-B), GABA reduces neuronal excitability and prevents runaway firing. Loss of inhibition or GABA deficits underlie epilepsy, anxiety disorders, and some developmental disorders. Many anxiolytics and sedatives (benzodiazepines, barbiturates, some anticonvulsants) enhance GABAergic signaling.

Glutamate — the main excitatory transmitter

Glutamate is the primary excitatory neurotransmitter and is essential for fast synaptic transmission, synaptic plasticity, learning, and memory (e.g., through NMDA and AMPA receptors). Excessive glutamatergic activity causes excitotoxicity and contributes to acute injuries (stroke, traumatic brain injury) and chronic neurodegeneration. Balance between glutamate and GABA is fundamental for healthy brain function.

Neurotransmitter imbalances disorders

Parkinson’s disease: degeneration of dopaminergic neurons → motor symptoms; dopamine replacement is mainstay therapy.
Depression & anxiety: complex, multi-system disorders involving serotonin, norepinephrine, dopamine, HPA axis, inflammation, and plasticity; SSRIs and SNRIs target monoamine systems but are not universal cures.
Schizophrenia: classic models involve dopaminergic hyperactivity in some pathways (positive symptoms) plus additional glutamatergic and GABAergic dysfunction; newer treatments explore non-dopamine strategies.
Epilepsy: hyperexcitability often involves glutamate/GABA imbalance; many antiepileptic drugs enhance GABA or reduce excitatory transmission.
Addiction: drugs of abuse hijack dopaminergic reward pathways and remodel synaptic plasticity in limbic circuits, creating compulsive drug-seeking.
Neurodevelopmental disorders: altered E/I (excitatory/inhibitory) balance (glutamate vs GABA) is reported in autism spectrum conditions and other neurodevelopmental syndromes.

Measuring and targeting neurotransmitters — clinical and research advances

Measuring neurotransmitter activity in humans is challenging. Techniques include PET imaging with receptor or transporter ligands, magnetic resonance spectroscopy (MRS) to estimate GABA/glutamate pools, and cerebrospinal fluid assays. Indirect functional measures (EEG, fMRI) complement biochemical tools. Therapeutically, pharmaceuticals modulate synthesis (L-DOPA), receptor activation/blockade (antipsychotics, benzodiazepines), reuptake (SSRIs, SNRIs), or degradation (MAO inhibitors, cholinesterase inhibitors). Gene and circuit-based therapies and neuromodulation (DBS, TMS) increasingly aim to restore healthy neurotransmitter function. Recent work highlights volume transmission and co-release phenomena that add complexity to classical synaptic models.

Key caveats: simple stories rarely tell the whole truth

Popular shorthand (e.g., “low serotonin causes depression” or “dopamine = pleasure”) is convenient but oversimplified. Contemporary reviews emphasize multifactorial causes for psychiatric and neurological disorders: network dysfunction, receptor and transport changes, plasticity, genetics, environment, immune and metabolic factors. Treatments that target neurotransmitters can be effective, but they are part of an integrated therapeutic approach including psychotherapy, lifestyle, and neuromodulation where appropriate.

Practical takeaways

Neurotransmitters are essential chemical messengers that control brain function.
Balance between excitatory (glutamate) and inhibitory (GABA) systems is crucial for stable brain activity. Monoamines (serotonin, norepinephrine, dopamine) modulate mood, arousal, motivation, and attention; many psychiatric drugs act on these systems.
Clinical conditions arise from complex interactions; neurotransmitter-targeted drugs help many people but do not fully explain disease causation.

References

Teleanu, R. I., et al. Neurotransmitters—Key Factors in Neurological and Psychiatric Disorders. Frontiers/PMC, 2022.
Sheffler, Z. M. Physiology, Neurotransmitters. StatPearls, 2023.
Moncrieff, J., et al. The serotonin theory of depression: a systematic umbrella review. Molecular Psychiatry, 2023.
Klein, M. O., et al. Dopamine: Functions, Signaling, and Association with Neurological Disorders. PMC review, 2018 (overview of dopamine biology).
Allen, M. J. GABA Receptor. StatPearls, 2023.
Özçete, Ö. D., et al. Mechanisms of neuromodulatory volume transmission. Nature Reviews, 2024.

Neurotransmitters